Identification of genes mediating lipophosphoglycan biosynthesis by functional complementation of Leishmania donovani mutants

Abstract

A powerful approach for identifying the genes involved in the infectious cycle of pathogens is functional genetic complementation. Here, the current status of this technology in Leishmania is reviewed, focusing on the genes involved in the biosynthesis of the unique parasite surface glycolipid, lipophosphoglycan (LPG). LPG plays multiple roles in the Leishmania infectious cycle, in both the sand fly vector and in establishing successful intracellular parasitism within the vertebrate macrophage. The emerging methods for generating LPG mutations and for recovering the affected gene(s) by complementation with an episomal genomic Leishmania DNA library are reviewed. The properties and probable roles of the first two genes identified by this methodology are discussed. These methods also show great promise in the search for genes affecting other virulence factors of Leishmania as well as in the identification of new drug-resistance loci.